Multidrug-Resistant Tuberculosis: A Global Threat

This assignment delves into the critical issue of multidrug-resistant tuberculosis (MDR-TB). It examines various aspects of this global health concern, including its transmission, resistance mechanisms, socioeconomic impact on patients, treatment challenges, and the role of BCG vaccination. The provided research articles offer insights into MDR-TB epidemiology, case reports, genetic variants associated with drug resistance, and potential solutions like plant-derived antimicrobials.

Running head: COMMUNICABLE DISEASES 1
Communicable Diseases
Student’s Name
Date of Submission

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Introduction
Multidrug resistant mycobacteria infections have been the biggest challenge in
microbiology and health sector. Generally, tuberculosis is a highly infectious disease caused by
several species of mycobacteria, specifically the Mycobacterium tuberculosis. This condition
causes many deaths because it majorly infects the respiratory system as well as many other
tissues like skin, kidneys and bones in advanced stages (Lange et al., 2014). Tuberculosis is
linked to many loss of lives annually via tuberculosis or tuberculosis-linked body conditions. The
spread of multi drug resistant tuberculosis occurs by being spread from infected carriers (either
in active or latent mode) to uninfected persons through the air. There have been high number of
mortalities as a result of mycobacterium tuberculosis infection because there are some people
who have no symptoms for this condition hence do not initiate treatment early enough. At this
stage, there is a need for the early medication to be initiated following the positive testing by
these subjects. According to Yuen et al., 2015, bearing in mind the complexity of
mycobacterium species, when giving medication (specifically the antibiotics) to the patients. A
big challenge however which faces the treatment process of tuberculosis is the emergence of
multidrug resistant tuberculosis strains. These strains of mycobacterium undergo several rounds
of mutations from time to time and hence they cannot respond to first line drugs. This challenge
is faced and felt by all stakeholders including the health practitioners, communities and the
government and hence the need for being addressed with due urgency (Meumann et al., 2015).
Therefore, this essay explores the problems of facing the treatment of bacterial infections with
focus on multidrug resistance in tuberculosis in Australia.

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Epidemiology
The mycobacterium pathogen is passed from a person who is infected to uninfected
person through sneezing and coughing, behaviors which spread pathogen droplets into the air.
The pathogen is ingested by a healthy person leading to the initial infection with tuberculosis,
where the pathogen spreads to several parts of the body under host immune system regulation
(Trauer & Cheng, 2016). The infection with tuberculosis pathogen occurs in two steps. The first
one is the latent step when the body is in a state of carrying the pathogen. The second one is the
active step, where the body is unable to suppress the pathogen anymore because it is too weak.
The transmission of tuberculosis pathogens occurs shortly following the patient exposuer to the
active form of tuberculosis. The mycobacteria cannot be transmitted through some behaviors like
sharing clothes, and bedding. This is because such pathogens die when they land on dry surfaces,
as opposed to moist surfaces that they prefer in the breathing system.
When the mycobacterium infectious particles are inhaled into an uninfected individual,
the particle moves to the respiratory tract and lands in the alveoli. The alveoli are critical in the
exchange of oxygen between the lungs, the blood and other tissues. As Subramani et al., 2017
states, although the immune system fights diseases, mycobacterium tuberculosis have cell walls
that offer them protection hence they evade the immune response and are not destroyed. During
normal host invasion by pathogens, macrophages are the immune cells which surround, engulf
and destroy the pathogen using innate immunological mechanisms. In case a patient previously
infected by another pathogen, like HIV gets exposed to mycobacterium tuberculosis, the
pathogen overwhelms the immune cells and makes the body weaker than it was initially. Active
tuberculosis infection causes a widespread distribution of the pathogen from the initial site of
infection, that is the alveoli, and spreads out into the blood circulation and lymphatic system. As

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Jenkins et al., 2014 reports, in the process, other several tissues in the body like the skin,
kidneys, bones, and reproductive system become infected increasing the pathogen load in the
host. The most commonly observed signs and symptoms in patients at active step of tuberculosis
infection may include weight loss, reduced appetite and fever among other signs. However, it is
surprising that there are some patients who are asymptomatic. As the patient sneeze and cough,
they spread the infectious materials of Mycobacterium tuberculosis into the tissues, and hence
more destruction of the lungs.
Screening of mycobacterium tuberculosis
According to Xu et al., 2017, Mycobacterium tuberculosis which is in latent step can be
tested using several methods to help in early diagnosis and hence initiate early treatment.
Mantoux test is able to detect tuberculosis infections as early as at two months following
pathogenic infection. Mantoux or skin test involves the injection of a chemical into the skin of
the forearm. If the patient develops a red wilt at the point of injection on the skin layers, then the
patient is infected by mycobacterium tuberculosis pathogens. However, using the Mantoux test,
it’s not possible to determine the stage of infection, that is, whether it is in latent or active step
(Fox et al., 2017). Some other screening methods that can be used are x rays, and acid fact
staining, which are commonly used in hospitals.
The multi-drug resistance tuberculosis
Having a clear understanding of the infection, diagnosis, treatment and control of
tuberculosis bacteria is very important. The mycobacterium tuberculosis bacteria contain unique
features from other bacteria types which makes its pathogenesis to be of special concern as
argued by Kendall et al., 2017. For instance, these bacteria have high levels of lipids in their cell
wall making them to resist cell wall degradation by antibiotics. The most commonly and

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effective test for this pathogen is the use of the acid-fast staining method for the presence
absence test. It has been noted that the mycobacterium tuberculosis bacteria have a long latency
period because it takes approximately 26 hours for its cell to divide, while other types of bacteria
take 6 hours (short latent period) for the bacterial cells to multiply. The main reason as to why
mycobacterium tuberculosis infects the respiratory system is because it is an aerobic pathogen.
As a result, the lungs have a rich supply of oxygen for exchange with the respiring tissues. A
number of the commonly observed multidrug resistance tuberculosis which are a global threat
are as a result of errors committed by physicians while others are cause by the negligence by the
patients who might fail to comply with medications. According to Tanimura et al., 2015, while
nearly most countries face problems with multidrug resistance, the most affected are the
developing countries due to low economic status that hinders them from effectively handling the
conditions. More specifically, Shekar et al., 2014 argues that the problems of multidrug resistant
tuberculosis strains are as a result of bacteria strains which have developed resistance to first line
antimicrobials, rifampicin and isoniazid, common drugs used as the first line drugs in
tuberculosis treatment. Molecular biology techniques have been widely used in exploring
research to counter this problem and more so the manner in which multi drug resistance
tuberculosis arises. Taking an example of isoniazid, drug resistance occurs when there are
mutations in either the inhA or katG genes of its genetic material. For the rifampicin, drug
resistance occurs when mutations develop on the beta subunit of the rpo gene on its DNA
molecule (Getahun et al., 2015). In order for bacteria to be resistant to several types or classes of
bacteria, there are several types of mutations which occurs in direct and indirect ways. This
enables the bacteria species to switch from those that are susceptible to drugs to those that are
not. During multi drug resistance tuberculosis bacteria tests, a positive standard of

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mycobacterium tuberculosis so that it can be used for comparison purposes. There are some
other factors which would lead to development of multi drug resistant bacterial strains in
tuberculosis and these include; previous medications, malabsorption and lack of proper
information (Lange et al., 2014). Other minor but common cause of drug resistance could be a
result of having problems poor sensitive laboratory diagnostic methods. In this case, the patients
might be unaware that they possess multi drug resistant tuberculosis strains and hence may fail to
get treatment as early as they are supposed to.
Apart from the usual diagnostic and failure to comply with medication, there are other
factors which predispose a patient to developing multi drug resistant tuberculosis as compared to
another patient. A good example is a situation where a person has HIV/AIDS which in most
cases makes the immune system to be weak. In the process of making frequent visits to the
hospitals, there is a higher likelihood of one developing multi drug resistance tuberculosis
because their immune system is already weak. It is worth noting that the patients who have
developed resistance to tuberculosis antimicrobials have only an option of using the second line
agents (Kendall et al., 2017). The second line antibiotics are very expensive and are more toxic
hence high mortality rates are observed especially on the patients who are susceptible to
tuberculosis drug resistances.
Patient outcomes on multidrug resistance tuberculosis
Once the first line agents have failed, using the second line drugs to treat tuberculosis is
economically unfavorable to patients. Apart from costs, these drugs are more toxic hence raising
the mortality rates among these patients, as stated by Du Toit et al., 2015. In case there is a
possibility of co-infection with other diseases like cancer, HIV/AIDS or hepatitis further
weakens their immune system leading to possibilities of deaths. It has been observed that patient

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with tuberculosis and HIV co-infection undergo poor drug malabsorption and thus high loads of
the pathogen. The patients undergo other costs which may hamper treatment are high transport
costs, accommodation, poor nutrition, and lack of productivity at workplaces, hence the need to
alleviate them from these costs (van den Hof et al., 2016). In the event that the person is
suffering from multi drug resistant tuberculosis, their low productivity means that their families
are negatively affected and children may drop out of school. According to Rodrigues et al., 2017,
patients who attempt to stop treatment when they feel better, need to know that the medical
charges of seeking tuberculosis treatment using second line drugs are more expensive, while the
toxic effects are so high as opposed to initial treatment.
World Health Organization response to multidrug resistance tuberculosis
The World Health Organization has recommended that Bacilli Calmette Guerin (BCG)
vaccine be used in regions where tuberculosis disease is most prevalent. The BCG vaccine is
made up of a weakened mycobacterium tuberculosis bacterium. Upon introduction into the body,
the weak pathogen induces production of antibodies. Later on, when the actual pathogen infects
the host, these antibodies will remember and mount an immunological response against the
pathogen. As Roy et al., 2014 argues, although BCG vaccine has a high efficacy, it could also be
affected by the geographical location of the patient as well as the age of the patient during
vaccination. Other treatment methods advocated for by the World health organization are TB
chemotherapy which include isoniazid, pyrazinamide, rifampicin and ethambutol (first line
drugs). In case the pathogen has become resistant against these first-line drugs, then the next
option is to initiate the second-line drugs on the parent.
However, the second-line drugs have more serious side effects because of their low
potency means that they need to be taken at higher doses.it is advisable that when tuberculosis

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treatment is being initiated, there is close monitoring and supervision by qualified health
professionals in order to ensure drugs compliance (Manson et al., 2017). It is common that some
patients may stop taking medications before the pathogen is cleared from the body. For a
complete cure, it is recommended that treatment be carried out for a period of between six to
nine months. There exists another method of treating mycobacterium tuberculosis infections,
which is less familiar known as the DOTS-Plus technique. This technique uses a direct method
of observing patients but on a short period of time. This method is commonly used in poor, rural
areas where hospital facilities are not available.
Development of multidrug resistance to mycobacterium tuberculosis
Multi drug resistance occurs through genetic alterations more specifically via
chromosomal mutations in the genes that encode the commonly used drug targets. The
accumulation of such chromosomal mutations in genes causes the insurgence of multidrug
resistance (Francis et al., 2014). When this happens, the mycobacterium tuberculosis bacteria
become insensitive to one or more and in this cases it is rifampicin and isoniazid. The patients
who multi drug resistance bacteria strains can only rely on second-line drugs like
fluoroquinolones or use injectable like kanamycin and amikacin. Studies by Rajendran &
Sethumadhavan, 2014 suggest that in order to counter multidrug mycobacterium tuberculosis
drug resistance, it is vital to have a clear understanding of the basic mechanism of action of first
line drugs. Here, isoniazid has been used as an example of common drugs that bacteria have
developed resistance against.
Isoniazid demonstrates two mechanism of action but based on the rate of bacterial cell
multiplication rate. First is that isoniazid being bactericidal agents which kills bacteria in vivo
within a short time, especially the fast-replicating cells. On the other hand, isoniazid acts in a

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bacteriostatic manner to eliminate the slow replicating bacteria strains. Since isoniazid is a
prodrug, it needs to be activated in order to be catalytically active. This activation is catalyzed by
the enzyme catalase peroxide homeoprotein G which then causes the blockage of mycolic acid
synthesis leading to destruction of the bacterial cell walls. Activation of isoniazid is a unique
process which only occurs in mycobacterium tuberculosis pathogens leading to the formation of
mycolic acid. The development of drug resistance against isoniazid by mycobacterium
tuberculosis is caused by mutations in the InhA gene.
Multi drug resistance in Australia
Tuberculosis is regarded as the most common communicable disease in the world. It is
interesting to note that Austria has the lowest prevalence of tuberculosis as a result of its good
public health systems. However, there are a few detected cases in the same country making the
mortality rates from Australia to be at a rate of 0.6 deaths for every 100,000 people (Australian
government department of health, 2016). The effects and prevalence of tuberculosis infections
occur frequently among the Aboriginals in Australia as compared to other ethnic groups due to
their low level socioeconomic status. This is because they have low self-esteem hence they can’t
afford basic hospital service. Moreover, since they live in isolation, they do not associate with
others nor seek treatment due to rich cultural beliefs. Despite the fact that Australia has for a long
time recorded a low rate of multidrug-resistant tuberculosis infections, it is a predictable pattern
to find that the indigenous Australians and Australians born from overseas have a higher disease
burned as compared to the non-indigenous Australians. During the earliest discovery of
tuberculosis in Australia, it was the leading cause of mortality and morbidity; indicating that the
government has made a lot of efforts to bring the disease to control. However, Roberts-
Witteveen et al., 2015 notes that as scientist struggle in microbial research and drug discovery,

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chemotherapy has been a scientific product which has made it possible to counter the rates of
spread of tuberculosis pathogens.
According to the reports from the Tuberculosis Control Program in Australia, there are
major plans in place which aim at reducing the rates of tuberculosis infection as well as lower the
transmission rates by use of improved tuberculosis diagnostic and treatment methods. According
to James and Allen, 2016, majority of the tuberculosis infections recorded among the minority
groups, a large proportion falls on the Australians who are born overseas, and the lesser
proportion falls on the indigenous Australians. Examples of migrant groups in Australia who
have common multidrug resistant Mycobacterium tuberculosis infections include those from
Nepal, India and China. It is worth noting that according to the reports by The Australian Society
for infectious Diseases, there is a possibility of previously controlled diseases re-emerging as a
result of drug resistance against initially effective drugs (Pacific beat, 2016). Moreover, the
Society for Infectious Diseases, warns that the development of multi drug resistant tuberculosis
strains is the most common just as the cases being observed in the Queensland region.
World Health Organization recognizes that after a long period since the declaration of
tuberculosis as a global health concern, there has been significant progress made to deal with its
treatment. On the other hand, there has been too little progress in terms of controlling the
multidrug resistant tuberculosis. The World Health Organization estimates that the overall cost
of treating multidrug resistant tuberculosis is more than one hundred times more than that of
those people susceptible to tuberculosis. This clearly means that there is an urgent need for the
department of public health and planning to come up with more effective educative, diagnostic
and treatment methods to deal with this menace before it spreads to the rest of the Australians
(El-Abaseri et al., 2015). The most common toxic effects during the use of second-line agents in

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tuberculosis are ototoxicity and hepatitis. The side effects require that there should be more
details in terms of clinical tests, monitoring and coming up with better therapeutic agents.
Conclusion
In summary, the issue of multi drug resistance tuberculosis presents serious problems to
the success of mycobacterium tuberculosis treatment efforts. Bearing in mind that the second line
mycobacterium tuberculosis drugs are expensive and having high toxicity, there are still
challenges in achieving proper treatment. Co-infection with other diseases has been found to
increase susceptibility to multidrug tuberculosis infections due to weakened immune system. The
ministry of health in Australia needs to formulate and implement preventive and early
tuberculosis treatment programs. As these programs run, they should be closely monitored to
find out whether they are actually achieving the intended purpose or not. Moreover, in Australia,
it is important to lay more emphasis to the health of the Indigenous populations who in most
cases are the victims of health disparities. The Australian government should also engage in
campaigns, even door to door and if possible integrate screening and treatment at either
affordable or no costs at all. Such efforts will make it possible to lower the transmission rates to
the healthy population. By adopting these strategies, the Australian government will be able to
cater for the health needs of its people who can be productive again and take care of their
families without overdependence on the government provisions.

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